Increasing numbers of patients are being identified as suffering from mitochondrial diseases. Such diseases display great diversity in clinical symptoms and morphological and biochemical characteristics. Although mtDNA mutations have been identified in many patients, there are presently no effective treatments. One method which has great potential for overcoming mutations in mtDNA-encoded proteins is to place a wild-type copy of the affected gene in the nucleus, and target the expressed protein to the mitochondrion to function in place of the defective mitochondrial protein. All proteins encoded in human mtDNA are hydrophobic, are located in the mitochondrial inner membrane, and have multiple membrane-spanning regions. It has been proposed that one of the reasons that these genes have been retained in mtDNA is that the proteins they encode are too hydrophobic to be expressed in the nucleus and transported into mitochondria. The Chlorophytic algae Chlamydomonas reinhardtii and Polytomella spp. Have several specific respiratory chain subunit genes encoded in their nuclear DNA, that in humans are encoded in the mtDNA. These algae will be used to study the transfer of genes of the respiratory chain subunits from the mtDNA to the nucleus. The sequences of the mtDNA and of genes for several nuclear DNA-encoded respiratory chain complex subunits will be determined and analyzed. The identification of structural features of these polypeptides that are important for their import into mitochondria should be applicable towards the development of genetic therapies for human diseases resulting from mutations in mtDNA-encoded polypeptide genes.